Synthesis method and application of asymmetric ether compound
By using a silver trifluoromethanesulfonate catalyst in air and at room temperature, the harsh conditions and cumbersome operation of asymmetric ether synthesis methods have been solved, realizing a highly efficient and simple synthesis of asymmetric ether compounds, which is suitable for the preparation of pharmaceuticals and pesticides.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- PHARMA SHANGHAI
- Filing Date
- 2026-01-12
- Publication Date
- 2026-05-01
AI Technical Summary
Existing methods for synthesizing asymmetric ethers are subject to harsh conditions, are cumbersome to operate, require strict protection, and have significant substrate limitations, making them unsuitable for industrial production.
Using stoichiometric silver trifluoromethanesulfonate (AgOTf) as a catalyst, benzyl halides react with benzyl alcohols in air atmosphere and at room temperature to generate asymmetric ether compounds, simplifying the operation process and improving the selectivity and efficiency of the reaction.
This method enables the efficient synthesis of asymmetric ether compounds under mild conditions, with a wide range of applicable substrates, high product purity, and simple process steps, demonstrating significant industrialization potential.
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Figure CN121949038A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing asymmetric ether compounds and their application in the preparation of drugs and pesticides. Background Technology
[0002] Asymmetric ethers are an important class of organic compounds with the general structural formula RO-R' (R ≠ R'). They have wide applications in the chemical industry as excellent solvents, key intermediates for pharmaceuticals, polymer monomers, and precursors for fine chemicals.
[0003] Traditional Williamson ether synthesis typically involves nucleophilic substitution reactions between alkoxide anions and haloalkanes. It generally requires strong bases (such as sodium hydride or potassium tert-butoxide) and high reaction temperatures, making the conditions harsh, resulting in low atom economy. Furthermore, it has poor compatibility with many base-sensitive functional groups (such as ester and cyano groups), making it difficult to apply to the synthesis of complex molecules.
[0004] To address this issue, other synthetic routes have been developed in this field, such as acid-catalyzed transetherification reactions. However, these methods still have significant limitations in terms of reaction selectivity (e.g., avoiding the formation of symmetrical ether byproducts) and universality with complex substrates (especially substrates containing heteroatoms or specific substituents), and reaction efficiency and product yield need to be further improved.
[0005] Silver salts, particularly silver trifluoromethanesulfonate (AgOTf), exhibit unique activity in promoting carbon-heterobonding reactions as highly efficient Lewis acid catalysts. They can promote ether bond formation by activating electrophilic reagents such as halogenated hydrocarbons or stabilizing reaction intermediates. However, existing AgOTf catalytic systems typically have the following limitations: to ensure catalyst activity and reaction selectivity, the relevant reactions generally need to be carried out under strictly anhydrous and oxygen-free environments (inert gas protection) and light-protected conditions. For example, CN113717033B employs a photocatalytic / nickel catalytic system that requires the isolation of oxygen. These stringent operational requirements not only increase equipment costs and safety risks but also make the reaction process cumbersome, hindering industrial production.
[0006] Therefore, developing a method for synthesizing asymmetric ether compounds that is mild, easy to operate, has a wide range of applicable substrates, requires no special protection, and is suitable for industrial production is an urgent and significant technical challenge in this field. Summary of the Invention
[0007] The present invention aims to overcome the problems of harsh conditions, cumbersome operation, strict protection requirements, and large substrate limitations in the existing asymmetric ether synthesis methods, and provides a method for synthesizing asymmetric ether compounds with readily available raw materials, mild conditions, simple operation, wide substrate applicability, and good yield.
[0008] To achieve the above objectives, the present invention adopts the following technical solution: A first aspect of the present invention provides a method for synthesizing asymmetric ether compounds.
[0009] The process includes the following steps: using a stoichiometric amount of silver trifluoromethanesulfonate as a catalyst, reacting the benzyl halide of formula (I) with the benzyl alcohol of formula (II) to generate the asymmetric ether compound of formula (III).
[0010] In the formula, X is chlorine or bromine. Ar1 is selected from: substituted or unsubstituted C6-C 10 Aryl, or 5- or 6-membered heteroaryl containing 1 to 3 cyclic heteroatoms selected from nitrogen, oxygen and sulfur; Ar2 is selected from: substituted or unsubstituted C6-C 10 Aryl, or 5- or 6-membered heteroaryl containing 1 to 3 cyclic heteroatoms selected from nitrogen, oxygen and sulfur; Furthermore, Ar1 and Ar2 are different from each other.
[0011] Preferably, the "substituted C6-C" 10 In the aryl group, the substituents are 1 to 3 groups independently selected from halogen atoms, C1-C4 alkyl groups, C1-C4 alkoxy groups, and cyano groups. The "heteroaryl" group is a 5-membered heteroaryl group, more preferably selected from: pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and thiazolyl groups; the heteroaryl group may optionally be substituted by 1 or 2 substituents independently selected from C1-C4 alkyl groups and halogen atoms.
[0012] More preferably, the "substituted C6-C" 10 "Aryl" is a phenyl group substituted with 1 to 3 halogen atoms. "Heteroaryl" is a group selected from 1-methyl-1H-pyrazole-4-yl, thiazolyl-4-yl, oxazol-4-yl, 1-methyl-1H-imidazolyl-4-yl, isoxazol-3-yl, and 3,5-dimethylisooxazol-4-yl.
[0013] Preferably, the amount of silver trifluoromethanesulfonate used is 1.5 to 2.5 equivalents of the molar amount of the compound of formula (I).
[0014] More preferably, the amount of silver trifluoromethanesulfonate used is 2.0 equivalents of the molar amount of the compound of formula (I).
[0015] Preferably, the reaction is carried out in an air atmosphere.
[0016] Preferably, the reaction is carried out at room temperature.
[0017] Preferably, the reaction is carried out under conditions where light protection is not required.
[0018] Preferably, the reaction is carried out in a solvent selected from dichloromethane, 1,2-dichloroethane, acetonitrile, tetrahydrofuran, or mixtures thereof.
[0019] Preferably, the reaction time is 12 to 16 hours.
[0020] Preferably, the post-processing method of the reaction includes: after the reaction is completed, filtering the reaction mixture and concentrating the filtrate.
[0021] A second aspect of the present invention provides the use of an asymmetric ether compound prepared by the synthetic method described in the first aspect of the present invention in the preparation of a pharmaceutical or pesticide.
[0022] Compared with the prior art, the present invention has the following beneficial effects: (1) Mild conditions and simple operation: The reaction can be carried out efficiently in air atmosphere and at room temperature, and there is no need to avoid light. It completely eliminates the strict requirements of traditional silver catalysis for inert gas protection and light avoidance, greatly simplifies the process and reduces equipment and safety costs.
[0023] (2) High efficiency and specificity of catalyst system: Using silver trifluoromethanesulfonate (AgOTf) with a specific stoichiometry as catalyst, it exhibits excellent catalytic activity and selectivity for this type of direct etherification reaction, which is the key to achieving mild conditions.
[0024] (3) Wide substrate applicability: It has good compatibility with aryl and various five-membered heteroaryl (such as pyrazole, thiazole, oxazole, imidazole and isoxazole), and can efficiently construct asymmetric ether compounds with diverse structures.
[0025] (4) The post-processing is simple and easy to purify: the crude product can be obtained by filtration and concentration after the reaction. The process steps are simple, the product purity is high, the overall yield is good, and it has significant potential for industrial scale-up. Attached Figure Description
[0026] Figure 1 This is the ¹H NMR spectrum of compound 4-((6-bromo-2,3-difluorobenzyloxy)methyl)-1-methyl-1H-pyrazole obtained in Example 1 of this invention.
[0027] Figure 2This is the 1H NMR spectrum (¹H NMR) of compound 4-((6-bromo-2,3-difluorobenzyloxy)methyl)thiazole obtained in Example 2 of this invention.
[0028] Figure 3 This is the 1H NMR spectrum (¹H NMR) of compound 4-((6-bromo-2,3-difluorobenzyloxy)methyl)oxazole obtained in Example 3 of this invention.
[0029] Figure 4 This is the ¹H NMR spectrum of compound 4-((6-bromo-2,3-difluorobenzyloxy)methyl)-1-methyl-1H-imidazol obtained in Example 4 of this invention.
[0030] Figure 5 This is the 1H NMR spectrum (¹H NMR) of compound 3-((6-bromo-2,3-difluorobenzyloxy)methyl)isoxazole obtained in Example 5 of this invention.
[0031] Figure 6 This is the 1H NMR spectrum (¹H NMR) of compound 4-((6-bromo-2,3-difluorobenzyloxy)methyl)-3,5-dimethylisoxazole obtained in Example 6 of this invention.
[0032] Figure 7 This is the 1H NMR spectrum (¹H NMR) of compound 3,5-dimethyl-4-((thiazolyl-4-ylmethoxy)methyl)isoxazole obtained in Example 7 of this invention.
[0033] Figure 8 This is the ¹H NMR spectrum of compound 3,5-dimethyl-4-((oxazol-4-ylmethoxy)methyl)isoxazole obtained in Example 8 of this invention.
[0034] Figure 9 This is the ¹H NMR spectrum of compound 3,5-dimethyl-4-((1-methyl-1H-pyrazole-4-ylmethoxy)methyl)isoxazole obtained in Example 9 of this invention. Detailed Implementation
[0035] This invention will be described in detail through the following embodiments, but the scope of protection of this invention is not limited to these embodiments. Those skilled in the art can make appropriate modifications without departing from the spirit and scope of this invention. Unless otherwise specified, the reagents and raw materials involved in the embodiments are commercially available, and all operations used are conventional techniques in the art or performed in accordance with the instructions.
[0036] Example 1: Synthesis of 4-((6-bromo-2,3-difluorobenzyloxy)methyl)-1-methyl-1H-pyrazole This example demonstrates a synthetic route using benzyl bromide and heteroaryl methanol as substrates, and the reaction formula is as follows:
[0037] Step 1: Preparation of raw material 6-bromo-2,3-difluorobenzyl bromide 6-Bromo-2,3-difluorobenzyl alcohol (5 g, 22.4 mmol), triphenylphosphine (5.3 g, 22.4 mmol), and carbon tetrabromide (7.4 g, 22.4 mmol) were added to acetonitrile (50 mL) and reacted at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure. The residue was extracted with ethyl acetate (EA) (100 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a colorless oily crude product. This crude product was purified by silica gel column chromatography (eluting agent: petroleum ether / ethyl acetate, elution gradient from 0% to 20% v / v) to give 3.8 g of 6-bromo-2,3-difluorobenzyl bromide as a colorless oily liquid, with a yield of 60.1%.
[0038] Step 2: Synthesis of the target asymmetric ether compound 6-Bromo-2,3-difluorobenzyl bromide (100 mg, 0.35 mmol), 1-methyl-4-(hydroxymethyl)pyrazole (40 mg, 0.35 mmol), and dichloromethane solvent (10 mL) were added to the reaction flask. AgOTf (180 mg, 0.70 mmol) was added to the mixture under stirring. The reaction system was then stirred for 16 hours under air atmosphere, at room temperature (approximately 25°C), without the need for light protection.
[0039] After the reaction was complete, the reaction solution was directly filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure to remove the solvent, yielding a yellow, oily crude product. This crude product was purified by silica gel column chromatography (eluting with petroleum ether / ethyl acetate, a gradient elution of 0-50% v / v) to give 50 mg of the white solid target compound 4-((6-bromo-2,3-difluorobenzyloxy)methyl)-1-methyl-1H-pyrazole, with a yield of 45.2%. The structure of the product was confirmed by nuclear magnetic resonance spectroscopy. Figure 1 ).
[0040] Example 2 Synthesis of 4-((6-bromo-2,3-difluorobenzyloxy)methyl)thiazole This example demonstrates a synthetic route using benzyl bromide and thiazole heteroaromatic methanol as substrates, and the reaction formula is as follows:
[0041] The starting materials 6-bromo-2,3-difluorobenzyl bromide (100 mg, 0.35 mmol), 4-hydroxymethylthiazole (40 mg, 0.35 mmol), and dichloromethane (10 mL) prepared in step 1 of Example 1 were added to the reaction flask. AgOTf (180 mg, 0.70 mmol) was added while stirring, and the reaction was carried out in air at room temperature without the need for protection from light for 16 hours.
[0042] After the reaction was complete, the reaction solution was directly filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure to remove the solvent, yielding a colorless, oily crude product. This crude product was purified by silica gel column chromatography (eluting with petroleum ether / ethyl acetate, a gradient elution of 0–45% v / v) to give 40 mg of the target compound 4-((6-bromo-2,3-difluorobenzyloxy)methyl)thiazole, a colorless, oily liquid with a yield of 35.7%. The structure of the product was confirmed by nuclear magnetic resonance spectroscopy. Figure 2 ).
[0043] Example 3 Synthesis of 4-((6-bromo-2,3-difluorobenzyloxy)methyl)oxazole This example demonstrates a synthetic route using benzyl bromide and oxygen-containing heterocyclic (oxazole) methanol as substrates, with the following reaction formula:
[0044] The starting materials 6-bromo-2,3-difluorobenzyl bromide (100 mg, 0.35 mmol), 4-oxazolyl methanol (35 mg, 0.35 mmol), and dichloromethane (10 mL) prepared in step 1 of Example 1 were added to the reaction flask. AgOTf (180 mg, 0.70 mmol) was added under stirring, and the reaction was carried out in air at room temperature without the need for protection from light for 16 hours.
[0045] After the reaction was complete, the reaction solution was directly filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure to remove the solvent, yielding a yellow oily crude product. This crude product was purified by silica gel column chromatography (eluting with petroleum ether / ethyl acetate, a gradient elution of 0–45% v / v) to give 45 mg of the target compound 4-((6-bromo-2,3-difluorobenzyloxy)methyl)oxazole, a colorless oily liquid, with a separation yield of 42.5%. The structure of the product was confirmed by nuclear magnetic resonance spectroscopy. Figure 3 ).
[0046] Example 4 Synthesis of 4-((6-bromo-2,3-difluorobenzyloxy)methyl)-1-methyl-1H-imidazolium This example demonstrates a synthetic route using benzyl bromide and imidazole heteroaromatic methanol as substrates, and the reaction formula is as follows:
[0047] The starting materials 6-bromo-2,3-difluorobenzyl bromide (100 mg, 0.35 mmol), (1-methyl-1H-imidazol-4-yl)methanol (39 mg, 0.35 mmol), and dichloromethane (10 mL) prepared in step 1 of Example 1 were added to the reaction flask. AgOTf (180 mg, 0.70 mmol) was added under stirring, and the reaction was carried out in air at room temperature without the need for protection from light for 16 hours.
[0048] After the reaction was complete, the reaction solution was directly filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure to remove the solvent, yielding a yellow, oily crude product. This crude product was purified by silica gel column chromatography (eluting with petroleum ether / ethyl acetate, a gradient elution of 0-50% v / v) to give 55 mg of the target compound 4-((6-bromo-2,3-difluorobenzyloxy)methyl)-1-methyl-1H-imidazolium, a white solid, with a yield of 49.5%. The structure of the product was confirmed by nuclear magnetic resonance spectroscopy. Figure 4 ).
[0049] Example 5 Synthesis of 3-((6-bromo-2,3-difluorobenzyloxy)methyl)isoxazole This example demonstrates that benzyl bromide can also react smoothly with heteroaryl methanols at different linkage sites (3-position) on the isoxazole ring, as shown in the following reaction formula:
[0050] The starting materials 6-bromo-2,3-difluorobenzyl bromide (100 mg, 0.35 mmol), 3-hydroxymethylisoxazole (35 mg, 0.35 mmol), and dichloromethane (10 mL) prepared in step 1 of Example 1 were added to the reaction flask. AgOTf (180 mg, 0.70 mmol) was added under stirring, and the reaction was carried out in air at room temperature without the need for protection from light for 16 hours.
[0051] After the reaction was complete, the reaction solution was directly filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure to remove the solvent, yielding a yellow oily crude product. This crude product was purified by silica gel column chromatography (eluting with petroleum ether / ethyl acetate, a gradient elution of 0-50% v / v) to give the target compound 3-((6-bromo-2,3-difluorobenzyloxy)methyl)isoxazole 35 mg, a colorless oily liquid, with a separation yield of 32.8%. The structure of the product was confirmed by nuclear magnetic resonance spectroscopy. Figure 5 ).
[0052] Example 6 Synthesis of 4-((6-bromo-2,3-difluorobenzyloxy)methyl)-3,5-dimethylisoxazole This example demonstrates that benzyl chlorides can react efficiently with classic aryl methanol (benzyl alcohol), expanding the range of halogenated compounds. The reaction formula is as follows:
[0053] 4-Chloromethyl-3,5-dimethylisoxazole (100 mg, 0.69 mmol), 6-bromo-2,3-difluorobenzyl alcohol (153 mg, 0.69 mmol), and dichloromethane (10 mL) were added to the reaction flask. AgOTf (355 mg, 1.38 mmol) was added under stirring, and the reaction was carried out in air at room temperature without the need for protection from light for 16 hours.
[0054] After the reaction was complete, the reaction solution was directly filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure to remove the solvent, yielding a yellow, oily crude product. This crude product was purified by silica gel column chromatography (eluting with petroleum ether / ethyl acetate, a gradient elution of 0-50% v / v) to give 114 mg of the target compound 4-((6-bromo-2,3-difluorobenzyloxy)methyl)-3,5-dimethylisoxazole, a white solid, with a yield of 50.1%. The structure of the product was confirmed by nuclear magnetic resonance spectroscopy. Figure 6 ).
[0055] Example 7 Synthesis of 3,5-dimethyl-4-((thiazol-4-ylmethoxy)methyl)isoxazole This embodiment realizes the cross-etherification reaction between two different heteroaryl fragments (isoxazole chloroproduct and thiazole methanol), and the reaction formula is as follows:
[0056] Add 4-chloromethyl-3,5-dimethylisoxazole (100 mg, 0.69 mmol), 4-hydroxymethylthiazole (79 mg, 0.69 mmol), and dichloromethane (10 mL) to the reaction flask. Add AgOTf (355 mg, 1.38 mmol) with stirring, and react for 16 hours in air at room temperature without the need for protection from light.
[0057] After the reaction was complete, the reaction solution was directly filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure to remove the solvent, yielding a yellow, oily crude product. This crude product was purified by silica gel column chromatography (eluting with petroleum ether / ethyl acetate, a gradient elution of 0–45% v / v) to give 60 mg of the target compound 3,5-dimethyl-4-((thiazolyl-4-ylmethoxy)methyl)isoxazole, a white solid, with a yield of 38.9%. The structure of the product was confirmed by nuclear magnetic resonance spectroscopy. Figure 7 ).
[0058] Example 8 Synthesis of 3,5-dimethyl-4-((oxazol-4-ylmethoxy)methyl)isoxazole This example demonstrates the successful reaction between isoxazole chlorinated derivatives and another oxygen-containing heterocyclic (oxazole) methanol, as shown in the following reaction formula:
[0059] Add 4-chloromethyl-3,5-dimethylisoxazole (100 mg, 0.69 mmol), 4-oxazolylmethanol (68 mg, 0.69 mmol), and dichloromethane (10 mL) to the reaction flask. Add AgOTf (355 mg, 1.38 mmol) under stirring, and react for 16 hours in air at room temperature without the need for protection from light.
[0060] After the reaction was complete, the reaction solution was directly filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure to remove the solvent, yielding a yellow, oily crude product. This crude product was purified by silica gel column chromatography (eluting with petroleum ether / ethyl acetate, a gradient elution of 0-50% v / v) to give 57 mg of the target compound 3,5-dimethyl-4-((oxazol-4-ylmethoxy)methyl)isoxazole, a colorless, oily liquid, with a yield of 40.1%. The structure of the product was confirmed by nuclear magnetic resonance spectroscopy. Figure 8 ).
[0061] Example 9 Synthesis of 3,5-dimethyl-4-((1-methyl-1H-pyrazole-4-ylmethoxy)methyl)isoxazole This embodiment achieved the etherification of isoxazole chloro derivatives with pyrazole methanol in high yield, demonstrating the good adaptability of the method of the present invention to nitrogen heterocycles. The reaction formula is as follows:
[0062] Add 4-chloromethyl-3,5-dimethylisoxazole (100 mg, 0.69 mmol), 1-methyl-4-(hydroxymethyl)pyrazole (77 mg, 0.69 mmol), and dichloromethane (10 mL) to the reaction flask. Add AgOTf (355 mg, 1.38 mmol) under stirring, and react for 16 hours in air at room temperature without the need for protection from light.
[0063] After the reaction was complete, the reaction solution was directly filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure to remove the solvent, yielding a yellow, oily crude product. This crude product was purified by silica gel column chromatography (eluting with petroleum ether / ethyl acetate, a gradient elution of 0-50% v / v) to give 91 mg of the target compound 3,5-dimethyl-4-((1-methyl-1H-pyrazol-4-ylmethoxy)methyl)isoxazole, a white solid, with a yield of 60.1%. The structure of the product was confirmed by nuclear magnetic resonance spectroscopy. Figure 9 ).
[0064] Control and optimization experiments 1. Reaction Atmosphere Control Experiment
[0065] Under the same material, catalyst dosage and reaction time as in step 2 of Example 1, a control experiment was set up, that is, the reaction conditions were changed from air atmosphere to strict nitrogen protection. Compared with Example 1, the control group did not produce the target product and a large amount of starting material was left over, proving that air atmosphere is a necessary condition for the reaction system to proceed.
[0066] 2. Control experiment under light-shielding conditions
[0067] Under the same material and air atmosphere as step 2 of Example 1, a control group was set up, in which the reactor was tightly wrapped with aluminum foil to completely block light. The results showed that the yield and purity of the control group were comparable to those under natural light conditions in Example 1. The operation of blocking light is not a necessary condition for this reaction, which further simplifies the operation process.
[0068] 3. Optimization experiment of catalyst (silver trifluoromethanesulfonate, AgOTf) dosage Under the same material, air atmosphere, and room temperature conditions as in step 2 of Example 1, the effect of AgOTf dosage on the reaction yield was systematically investigated, and the results are shown in Table 1.
[0069]
[0070] As shown in the table above, the amount of AgOTf significantly affects the reaction efficiency. When the amount is below 1.5 equivalents, the yield is low; the yield reaches its maximum at 2.0 equivalents; further increasing the amount slightly decreases the yield. Therefore, using 2.0 equivalents of AgOTf is the preferred condition for this reaction.
[0071] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.
Claims
1. A method for synthesizing asymmetric ether compounds, characterized in that, Includes the following steps: Using stoichiometric amounts of silver trifluoromethanesulfonate as a catalyst, the benzyl halide shown in formula (I) reacts with the benzyl alcohol shown in formula (II) to generate the asymmetric ether compound shown in formula (III). ； In the formula, X is chlorine or bromine. Ar 1 Selected from: substituted or unsubstituted C6-C 10 Aryl, or 5- or 6-membered heteroaryl containing 1 to 3 cyclic heteroatoms selected from nitrogen, oxygen and sulfur; Ar 2 Selected from: substituted or unsubstituted C6-C 10 Aryl, or 5- or 6-membered heteroaryl containing 1 to 3 cyclic heteroatoms selected from nitrogen, oxygen and sulfur; And Ar 1 with Ar 2 They are different from each other.
2. The synthesis method according to claim 1, characterized in that, The amount of silver trifluoromethanesulfonate used is 1.5 to 2.5 equivalents of the molar amount of the compound of formula (I).
3. The synthesis method according to claim 2, characterized in that, The amount of silver trifluoromethanesulfonate used is 2.0 equivalents of the molar amount of the compound of formula (I).
4. The synthesis method according to claim 1, characterized in that, The reaction was carried out in an air atmosphere.
5. The synthesis method according to claim 1, characterized in that, The reaction is carried out at room temperature.
6. The synthesis method according to claim 1, characterized in that, The reaction is carried out under conditions where light protection is not required.
7. The synthesis method according to claim 1, characterized in that, The reaction is carried out in a solvent selected from dichloromethane, 1,2-dichloroethane, acetonitrile, tetrahydrofuran, or mixtures thereof.
8. The synthesis method according to claim 1, characterized in that, The reaction takes 12 to 16 hours.
9. The synthesis method according to claim 1, characterized in that, The post-processing method of the reaction includes: after the reaction is completed, filtering the reaction mixture and concentrating the filtrate.
10. Use of the asymmetric ether compound prepared by the synthetic method according to any one of claims 1 to 9 in the preparation of a drug or pesticide.